1. Field of the Invention
The invention disclosed herein relates generally to shakers for microplates, small diameter test tubes, and like-configured fluid containers, and more particularly to an electromagnetic vibratory microplate and multi-tube rack shaker of simplified construction for imparting vertical vibration to one or more microplates or multi-tube racks containing a multitude of biological or chemical samples, such vertical vibration being of sufficient amplitude to cause effective and thorough mixing of the contents of each microplate well or tube.
2. Description of the Background
The processing of biological specimens or chemical products in laboratories often requires the mixing of analytes within a container in order to carry out a desired reaction. Such containers have often comprised beakers or flasks whose contents were traditionally mixed by either manually shaking the beaker or flask, or using a stirring rod. Other mixing apparatus have included a Teflon coated magnet placed within a beaker or flask and driven magnetically in a rotary motion to mix the beaker or flask contents. Unfortunately, manually shaking the beaker or flask provides insufficient means to control the mixing of the contents and easily results in laboratory technicians accidentally dropping the container and ruining the sample. Likewise, the use of stirring rods has required that the laboratory technician either thoroughly wash the rod between specimens in order to avoid cross-contamination, or throw away and replace disposable rods for applications with large numbers of specimens, making the rapid mixing of large numbers of specimens highly impractical.
In order to overcome these shortcomings, motor driven orbital shakers were developed which enabled a laboratory technician to place a beaker or flask on a motor driven platform that would cause the beaker or flask to travel in a continuous orbit to mix its contents. So long as the diameter of the beaker or flask holding a sample is greater than the orbit diameter of the platform, mixing of the contents will occur. For example, as shown in the schematic view of a prior art orbital mixer of FIG. 1a, the center of the flask travels in an orbital path equivalent to the orbit of the platform, and the centrifugal forces on the liquid will reverse every 180xc2x0 to provide adequate mixing of the contents.
However, as the number of specimens needed to be analyzed in a given time period has grown, the quest for efficiency in the processing of such specimens has resulted in smaller and smaller sample sizes being studied, and thus smaller and smaller containers for holding those samples. Unfortunately, as smaller sized beakers and flasks were used, those orbital shakers having an orbit diameter that was larger than the beaker or flask diameter were shown to be ineffective for mixing the contents. For example, as shown in the schematic view of a prior art orbital mixer of FIG. 1b, a beaker or flask having a diameter that is smaller than the orbit diameter of the mixer simply travels in the shaker""s orbit, and centrifugal forces drive the liquid contained within the beaker or flask against the side of the container which is furthest from the center of orbit. If there are any suspended solids in the liquid, they will likewise be driven against the outside wall of the container, and fail to mix with the solution. In order to alleviate this problem, a few orbital shakers have been made available having orbit diameters of as little as xe2x85x9xe2x80x3.
As the need for processing greater numbers of samples in shorter amounts of time continued to grow, microplates were developed to hold multiple samples of a chemical or biological material to be analyzed in a single, compact structure having a rectangular grid of a large number of distinct xe2x80x9cwells.xe2x80x9d Such microplates are available today in 96-well, 384-well, and even 1536-well configurations. Likewise, racks of small diameter tubes have been developed providing a similar array of specimen-holding chambers. Such tube racks are available in up to 96-tube configurations. Obviously, the greater the number of wells or tubes in a standard microplate or rack footprint, the smaller the diameter of the well or tube, such that for microplates and tubes having chamber diameters of far less than xe2x85x9xe2x80x3, an orbit of far less than xe2x85x9xe2x80x3 would likewise be required in order to ensure proper mixing. As was true with orbital mixers for large flasks, the contents of such a small diameter tube rotating in an orbit larger than its own diameter are difficult to mix. Using an orbit larger than the well or tube diameter causes the liquid contents to move to the outside of the orbit and rise up the inner wall of the tube which is closest to the outside radius of the orbit. The contents of the tube begin to spin inside the tube with a relatively small amount of relative motion (or shearing) between adjacent layers of fluid within the walls of the tube. As the orbital speed is increased, the liquid in the tube is forced outward by centrifugal force, rising up the inner wall of the tube until it spills over the top. Given the orbit diameter limitation of only xe2x85x9xe2x80x3, traditional horizontal orbital shakers have thus been ineffective in shaking microplates and tube collections having such small diameter chambers.
Given the failure of traditional orbiting mixing apparatus to provide an effective means of mixing the contents of small well microplates and small diameter tubes, attempts have been made to provide mixing apparatus specifically configured for mixing the contents of microplate wells, but unfortunately have also met with little success. For example, U.S. Pat. No. 3,635,446 to Kurosawa et al. discloses a microplate shaking device using an eccentric motor to uncontrollably vibrate a microplate holding plate through a horizontal plane. Likewise, U.S. Pat. No. 4,102,649 to Sasaki discloses a microplate shaker device which pivotally mounts a microplate to a vibration plate, and slidably mounts the microplate atop a number of props. The vibration plate is caused to vibrate by either an electromagnet or an eccentric wheel in a nonlinear, horizontal manner. Further, U.S. Pat. No. 4,264,559 to Price discloses a mixing device for a specimen holder comprising two springlike metal rods upon which a specimen holder is mounted, the rods being fixed at one end in a vertical block, and a weight positioned adjacent the opposite end of the rods. Manually plucking one of the rods imparts a xe2x80x9cpendulum-likexe2x80x9d vibration to both rods, and thus to the specimen holder. Finally, U.S. Pat. No. 5,921,477 to Tomes et al. discloses an agitating apparatus for a xe2x80x9cwell plate holderxe2x80x9d which comprises a vertically-oriented reciprocating saw as a means for vertically shaking a multi-well plate, and provides agitating members comprising small diameter copper or stainless steel balls within each well.
Unfortunately, none of the known prior art devices have been able to provide controlled, vertical vibration to a microplate or collection of small diameter tubes in order to create vertical vibrational motion of sufficient turbulence to thoroughly mix the well or tube contents.
Furthermore, U.S. Pat. No. 5,427,451 to Schmidt discloses a mixer which utilizes a complex, microprocessor-controlled circuit to provide oscillatory drives comprised of permanent magnets and drive coils juxtaposed therewith, with each coil being independently energized by separate variable frequency sources. The drive circuits are configured to alternately attract and repel the permanent magnets so as to provide the oscillatory motion, thus requiring actuation of the drive coils at all times during operation of the mixer. Such a construction is highly complex, requiring precise control of the timing of each drive cycle, and exhibits high energy requirements for its operation. It would be highly advantageous to provide a simplified mixing construction that has a lower energy requirement, but that can still provide consistent, reliable mixing through linear vibration of test specimen containers.
It would therefore be advantageous to provide an electromagnetic, linear shaker of simplified construction which will ensure the efficient linear vibrational mixing of the contents of microplates and small diameter tubes, while keeping suspended solids truly suspended during the mixing cycle.
It is, therefore, an object of the present invention to provide a microplate and multi-tube rack shaker which avoids the disadvantages of the prior art.
It is another object of the present invention to provide a microplate and multi-tube rack shaker which can efficiently mix the contents of microplates and specimen tubes of all sizes while keeping suspended solids truly suspended during the mixing cycle.
It is yet another object of the present invention to provide a microplate and multi-tube rack shaker which enables the contents of a microplate and specimen tube to be properly mixed in a shorter amount of time than has been previously performed by prior art devices.
It is still yet another object of the present invention to provide a microplate and multi-tube rack shaker which enables the effective mixing of the contents of a plurality of microplates and multi-tube racks during a single mixing process.
It is even yet another object of the present invention to provide a microplate and multi-tube rack shaker of simplified design over prior art devices which ensures thorough mixing of the well and tube contents irrespective of the diameter of the wells and tubes.
It is still yet another object of the present invention to provide a microplate and multi-tube rack shaker of a more compact size than has been previously available in prior art shakers to enable such a shaker to be readily placed within a refrigerator or incubator for temperature-sensitive mixing applications.
It is even yet another object of the present invention to provide a microplate and multi-tube rack shaker of simplified construction that provides thorough mixing of the microplate contents through vibration directed solely in the vertical direction.
It is still even yet another object of the present invention to provide a microplate and multi-tube rack shaker which consistently applies a controlled vertical vibration to the contents of the microplate wells or tubes so as to create sufficient turbulence within each well or tube to ensure adequate mixing.
It is still even yet another object of the present invention to provide a microplate and multi-tube rack shaker having means for adjusting the amplitude of vibration to a sufficient level to vertically displace the entire contents of each well and tube during each vibration cycle.
It is still even yet another object of the present invention to provide a microplate and multi-tube rack shaker having a static indicia of amplitude of vibration attached to a microplate or multi-tube rack support tray on the shaker.
In accordance with the above objects, an electromagnetic vibratory microplate and multi-tube rack shaker is disclosed of simplified design and improved mixing capability over previously known shaker devices. The electromagnetic vibratory microplate and multi-tube rack shaker of the instant invention comprises an electromagnetic drive assembly vertically mounted within a rigid base and operatively connected to a microplate and multi-tube rack support platform. The support platform is in turn resiliently supported by a plurality of horizontally arrayed leaf springs. During operation, the electromagnet is rapidly energized and de-energized causing an armature of the drive assembly to be pulled in and released up to 7,200 times per minute, in turn deflecting the leaf springs in the vertical direction and imparting a reciprocating vertical vibration to the support platform and the microplates or multi-tube racks held thereon. Means are provided for adjusting the amplitude of the vibration as necessary to enable the entire volume of liquid within each well or tube to be vertically displaced within the well or tube during each vibration cycle, thus ensuring thorough mixing of the contents of each well or tube irrespective of its diameter, while keeping suspended solids truly suspended during the mixing cycle. Also provided is a static indicia of amplitude of vibration fixedly mounted on the support platform to enable the user to determine the optimal vibrational amplitude to use for a particular series of microplates or multi-tube racks being vibrated.
It should also be noted that the leaf spring members are entirely responsible for moving the support platform in the reverse direction from which it is driven by the electromagnet. Thus, the electromagnet need only be energized during half of each vibration cycle, thus eliminating the need for a permanent magnet within the drive assembly and reducing the energy required to operate the assembly.